Context: Students may develop academic burnout due to various factors, especially in stressful fields. This may cause educational and occupational negative impacts. Aims: The present study was an investigation of the relationship of motivation, self-efficacy, stress, and academic performance with academic burnout among paramedical and nursing students. Setting and Design: This descriptive-analytic study was conducted in Qom University of Medical Sciences. Materials and Methods: In the present study, 264 nursing and paramedical undergraduate students were selected through simple randomization. Demographic questionnaire, Maslach Burnout Inventory, Academic Stress Questionnaire (ASQ), Academic Self-efficacy Questionnaire (ASQ), and Academic Motivation Scale were used for data collection. The average of university course grades was used as the academic performance scale. Statistical Analysis Used: Data were analyzed by linear regression analysis and descriptive statistics including mean, standard deviation, and frequency. Results: The mean score of academic burnout was 28. 52 ± 15. 84. The results of regression analysis in univariate model showed that all subscales of academic performance variables, i. e., academic motivation, academic self-efficacy, and academic stress of students, were related to academic burnout (P < 0. 05). It was also found that internal motivation, no motivation, and assurance of self-ability to manage family and work were the most important factors in burnout, and 50% of variance changes was determined in academic burnout (r = 0. 71, r 2 = 0. 50). Conclusion: Based on the results of this study, internal motivation, amotivation, and family work management were identified as the most important decreasing factors on academic burnout. Therefore, promoting academic motivation; recognizing and applying the skills of family– work management; and recognizing the factors affecting stress, motivation, self-efficacy, and academic performance cause students to be protected against academic burnout.